Local anaesthetic agents Dr.Khaled Radaideh September 18 Dr. Med. Khaled Radaideh

Lecture Objectives: The Pharmacology of Local Anaesthetic Agents 1.Definition 2. Classification of Local Anaesthetic Agents 2.1. Comparison between the two Classes. 3. Mode of action 4. Preparation of Local Anaesthetic Agents September 18 Dr. Med. Khaled Radaideh

Lecture Objectives 5. Addition of Vasoconstrictors 5.1. Indications and Contraindications and Dosage. 5.2. How can I prepare Adrenaline 1:200000? 6. Clinical uses of local anesthetic agents 7. Lidocaine 8.Toxicity (Causes, Prevention and Treatment) 8.1. Systemic Toxicity September 18 Dr. Med. Khaled Radaideh

The molecule of the clinically useful LA agents consists of The Pharmacology of Local Anaesthetic Agents (LA) Local anaesthetic agents can be defined as drugs, which are used clinically to produce reversible loss of sensation in a circumscribed area of the body. Classification : The molecule of the clinically useful LA agents consists of A tertiary amine attached to an Aromatic ring by an Intermediate chain. September 18 Dr. Med. Khaled Radaideh

Classification of LA Agents There are 2 classes of local anaesthetic drugs defined by the nature of the intermediate chain. The ester LA agents include cocaine, procaine, and chloroprocaine The amide LA agents include lidocaine, prilocaine, bupivacaine, etidocaine, mepivacaine September 18 Dr. Med. Khaled Radaideh

There are important practical differences between these 2 groups of LA agents Esters are relatively unstable in solution Amides are relatively stable in solution Esters are rapidly hydrolysed in the body by plasma cholinesterase (and other esterases) Amides are slowly metabolised by hepatic amidases and Esters: One of the main breakdown products is para-amino benzoate (PABA) which is associated with allergic phenomena and hypersensitivity reactions Amides: hypersensitivity reactions to amide local anaesthetics are extremely rare In current clinical practice esters have largely been superseded by the amides. September 18 Dr. Med. Khaled Radaideh

Mode of action-Membrane structure September 18 Dr. Med. Khaled Radaideh

B.HCl + HCO3 <--> B + H2CO3 + Cl- Mode of action After injection, the tertiary amine base is liberated by the relatively alkaline pH of tissue fluids: These effects are due to blockade of sodium channels, thereby impairing sodium ion flux, across the membrane. B.HCl + HCO3 <--> B + H2CO3 + Cl- In clinical practice, local anaesthesia may be influenced by the local availability of free base (B), as only the unionised portion can diffuse through the neuronal membrane. Thus, local anaesthetics are relatively inactive when injected into tissues with an acid pH (e.g. pyogenic abscess), which is presumably due to reduced release of free base. September 18 Dr. Med. Khaled Radaideh

Preparations of LA LA agents are usually acid (pH range 4.0-5.5) and contain reducing agent (e.g. sodium metabisulphite) to enhance the stability of added vasoconstrictors preservative and a fungicide September 18 Dr. Med. Khaled Radaideh

What does 1% Lidocain mean? The dilute preparations are presented as percentage (%)solutions of LA. A solution expressed as 1% contains 1g substance in each 100mls 1 g in 100 ml = 1000mg in 100 ml 10 mg in 1 ml The number of mg/ml can easily be calculated by multiplying the percentage strength by 10. Therefore a 0.25% solution of lidocaine contains 2.5mg/ml of solution (10 * 0.25=2.5 mg /ml) September 18 Dr. Med. Khaled Radaideh

vasoconstrictors Most LA produce some degree of vasodilation, and they may be rapidly absorbed after local injection. vasoconstrictors decrease the systemic toxicity and increase the safety margin of local anaesthetics by reducing their rate of absorption vasoconstrictors are frequently added to LA to enhance their potency and prolong their duration of action Adrenaline is the most commonly used vasoconstrictor in concentrations ranging from 1 in 80,000 to 1 in 300,000 September 18 Dr. Med. Khaled Radaideh

How can I prepare Adrenaline 1:200000? Adrenaline dilution 1:200000 means 1 g in 200000 ml = 1000 mg in 200000 ml 1 mg in 200 ml = 0.1 mg in 20 ml 1:80000…………..= 0.1 mg in 8 ml Plain mg/Kg With Adrenaline mg/Kg Lidocaine 3 7 Prilocaine 6 9 Bupivacaine 2 September 18 Dr. Med. Khaled Radaideh

contraindication for Adrenaline containing local anaesthetic agents: agents Absolute contraindication (should never be used) for: 1.infiltration around end-arteries i.e. ring block of fingers, penis or other areas with a terminal vascular supply as the intense vasoconstriction may lead to severe ischaemia and necrosis. 2. Intravenous regional anaesthesia (IVRA)  Relative contraindication: 1.Patient with severe hypertension · 2.General anaesthesia with halothane September 18 Dr. Med. Khaled Radaideh

Clinical Uses of Local Anaesthetics 1. Topical Anaesthesia 2. Infiltration Anaesthesia 3. Peripheral Nerve Blockade 4. Intravenous regional anaesthesia (IVRA) 5. Spinal Anaesthesia 6. Extradural Anaesthesia September 18 Dr. Med. Khaled Radaideh

1: Topical Anaesthesia LA may be applied to the skin, the eye, the ear, the nose and the mouth as well as other mucous membranes. most useful and effective: Lidocaine (i.e.gel 2%) and prilocaine(i.e.EMLA)   2: Infiltration Anaesthesia provide anaesthesia for minor surgical procedures. commonly used Amide LA are (Lidocaine prilocaine,mepivacaine and Bupivacaine)., The site of action is at unmyelinated nerve endings and onset is almost immediate September 18 Dr. Med. Khaled Radaideh

3: Intravenous regional anaesthesia (IVRA) IVRA (BIER s Block) analgesia for minor surgical procedures. The local anaesthetic agent is injected into a vein of a limb that has been previously exsanguinated and occluded by a tourniquet. The site of action is probably the unmyelinated nerve fibres, Prilocaine and Ldocaine are commonly used. Bupivacaine and etidocaine should never be used for IVRA! They are significantly protein bound and once the tourniquet is released there is a risk of cardiotoxicity. Several deaths have been reported during IVRA with bupivacaine. September 18 Dr. Med. Khaled Radaideh

4: Peripheral Nerve Blockade : Regional anesthetic procedures that inhibit conduction in fibers of the peripheral nervous system. It can be devided into: Minor nerve blocks involve the blocking of single nerve entities such as the inferior alveolar nerve, mental nerve, ulnar or radial nerve. Major nerve blocks involve the blocking of deeper nerves or trunks with a wide dermatomal distribution (e.g. brachial plexus blockade). The commonly used LA agents are: Lidocaine, prilocaine, mepivacaine, and bupivacaine. September 18 Dr. Med. Khaled Radaideh

5: Extradural Anaesthesia:LA agent injected in the epidural space between the dura mater and the Lig.Flavum. usually used mainly isobaric Bupivacaine 0.5% or lidocaine (2.0%) 6.: Spinal Anaesthesia injction directly into the cerebrospinal fluid (subarachnoid space) produces spinal anaesthesia. commonly used : mainly hyperbaric Bupivacaine 0.5% or lidocaine (5%) September 18 Dr. Med. Khaled Radaideh

Lidocaine Lidocaine, the first amino amide-type local anesthetic, was developed first by Nils Löfgren and Bengt Lundqvist in 1943 and first marketed in 1948. Lidocaine Solutions 0.5, 1, 1.5 and 2% contain lidocaine hydrochloride 5, 10, 15 and 20 mg/mL, respectively. Solutions with epinephrine contain (1:100,000) or 0 (1:200,000) epinephrine. September 18 Dr. Med. Khaled Radaideh

Lidocaine Lidocaine use in anesthesia can be explained by the fact that it alters depolarization in neurons, by blocking the fast voltage gated sodium (Na+) channels in the cell membrane. With sufficient blockade, the membrane of the presynaptic neuron will not depolarize and so fail to transmit an action potential, leading to its anesthetic effects. Careful titration allows for a high degree of selectivity in the blockage of sensory neurons, whereas higher concentrations will also affect other modalities of neuron signalling. September 18 Dr. Med. Khaled Radaideh

Lidocaine Lidocaine is a local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic, and in minor surgery. September 18 Dr. Med. Khaled Radaideh

Toxicity from Local Anaesthetic Drugs when excessive blood levels occur. usually due to: Accidental rapid intravenous injection. Rapid absorption, such as from a very vascular site ie mucous membranes. Intercostal nerve blocks will give a higher blood level than subcutaneous infiltration, whereas plexus blocks are associated with the slowest rates of absorption and therefore give the lowest blood levels. Absolute overdose if the dose used is excessive. September 18 Dr. Med. Khaled Radaideh

Signs and Symptoms of LA Toxicity It involves the CNS and CVS. In general (CNS) is more sensitive to LA than the CVS. Therefore CNS manifestations tend to occur earlier. Brain excitatory effects occur before the depressant effects. CNS signs & symptoms Early or mild toxicity: light-headedness, dizziness, tinnitus, circumoral numbness, confusion and drowsiness. Patients often will not volunteer information about these symptoms unless asked. Severe toxicity: tonic-clonic convulsion leading to progressive loss of consciousness, coma, respiratory depression, and respiratory arrest. September 18 Dr. Med. Khaled Radaideh

CVS signs & symptoms Early or mild toxicity: if LA with Adrenaline tachycardia with Hypertension If no Adrenaline : bradycardia with hypotension Severe toxicity: Usually about 4 - 7 times the convulsant dose needs to be injected before CV collapse occurs. Collapse is due to the depressant effect of the LA acting directly on the myocardium (e.g. Bupivacaine) Severe and intractable arrhythmias can occur with accidental iv injection. September 18 Dr. Med. Khaled Radaideh

Essential Precautions and Treatment Precautions: Secure intravenous access before injection of any dose that . Always have adequate resuscitation equipment and drugs available before starting to inject. Treatment: stop the injection and assess the patient. Call for help while treating the patient Treatment is based on the A B C D of Basic Life Support Ensure an adequate airway, give O2 in over facemask . Ventilate the patient if there is inadequate spontaneous respiration Intubation : if the patient is unconscious and unable to maintain an airway. September 18 Dr. Med. Khaled Radaideh

Treatment of circulatory failure with I.V fluids and vasopressors: Ephedrin : If not available or not effective in correcting the hypotension ….Adrenaline Treat arrhythmias. Start chest compressions if cardiac arrest occurs. Treat Convulsions with anticonvulsant drugs (Diazepam 0.2-0.4mg/kg , Thiopentone 1-4 mg/kg September 18 Dr. Med. Khaled Radaideh